The role of enabled (ena) a putative substrate of the Abl protein tyrosine kinase will be investigated. The Drosophila Abl gene is the homolog of the mammalian c-abl proto-oncogene which has been implicated in chronic myelogenous leukemia and acute lymphoblastic leukemia. Functional regions of the ena protein will be identified by generating and sequencing mutant ena alleles. Mutant ena proteins will then be produced and tested for phosphorylation by the Abl tyrosine kinase and for binding to SH2 and SH3 domains with in vitro assays. A genetic screen win be carried out to identify novel genes involved in Abl mediated signal transduction that dominantly suppress the ena/dachs trans- heterozygous phenotype. Additionally, somatic clones with null mutations in ena will be generated to examine its role in development of the leg. Understanding the function of the Abl mediated signaling pathway in normal development may provide additional insight into its molecular mechanisms in neoplastic transformation.